Genetically altered pigs make human blood component

Using genetic engineering techniques, biologists have developed pigs that produce human hemoglobin, the essential oxygen-carrying component of blood.

Experts called the achievement a milestone in the effort to find a substitute for blood that could be used in all types of transfusions and might offer advantages over the donated blood now used.

A blood substitute could be stored for months instead of weeks, would be free of any risk of human infection and could be transfused into anyone without the need for blood typing and matching.

Officials of a small biotechnology company, DNX Inc. of Princeton, N.J., said they had developed three pigs that produce human hemoglobin, the substance in the red blood cells that transports oxygen throughout the body.

When the pigs were day-old embryos, the scientists injected sets of two genes that make human hemoglobin, and now, about 15 percent of the pigs' hemoglobin is human.

It is one of a very few times that scientists have put human genes into large animals and seen them function successfully.

The company's officials will outline the work today at a scientific meeting in Anaheim, Calif., and will describe what they regard as equally important: the discovery of a method of purifying the human hemoglobin produced.

The extracted hemoglobin has not been tried in humans, and it might not succeed. But DNX has given research data to the Food and Drug Administration and plans to apply this year for approval of human trials.

The company said it would take at least five years to complete research and testing of pig-produced hemoglobin, and there are also serious questions that will have to be overcome about the safety of using hemoglobin extracted from animals for human FTC transfusion.

But experts nevertheless praised the achievement.

"I think this is an exciting development," said Dr. Robert Winslow, chief of the blood research division of the Army's Letterman Institute of Research in San Francisco.

"Military doctors believe a solution to this problem of making a blood substitute that can carry oxygen would have saved the lives of 10,000 soldiers in Vietnam," he said. "Soldiers bleed to death on the battlefield, where you can't get blood to them, and before you can get them back to where they can be transfused."

Among the safety questions are whether some animal viruses might escape the purification process and cause illness in humans and whether cellular debris missed in purification could cause kidney damage or allergic reactions.

The DNX experiments began with the two human genes that control the body's production of hemoglobin. Researchers injected copies of the human genes into embryos taken from a donor pig. The embryos then were inserted into the womb of a second pig. They grew to term and were born.

Only about five in 1,000 of the transfers succeeded, but three pigs have been born with the human gene in their bodies in the last few years, the last one in February.

Research into breeding has begun, but DNX officials declined to discuss the program in detail. In theory, all progeny of such breeding would carry the human genes.

The altered pigs produce red blood cells that contain either pig he moglobin or human hemoglobin. So far, about 15 percent of the cells have the human type, but company officials say they expect to be able to raise the share to 50 percent.

Blood drawn from the pigs is put through a purification system that separates the human hemoglobin from pig hemoglobin by distinguishing their molecular electric charges.

It is the discovery of this purification technique that company officials believe is as significant as the creation of pigs carrying human hemoglobin.

The main advantages of making human hemoglobin in animals are related to red blood cells. These cells are containers that carry hemoglobin through the body as it absorbs oxygen in the lungs and delivers it to all cells.

But red cells are made of living membranes that are perishable. Outside the body they must be refrigerated, and even so are considered spoiled after about a month.

The red cells also bristle with an array of defensive molecules, and the reactions of these in the body is what makes blood typing and matching necessary.

But when hemoglobin is used alone, and purification is effective, there are no defensive molecules.

In addition, hemoglobin is a chemical rather than a living cell and so may be stored for months, or even longer if freeze-drying experiments prove successful.

When put into the bloodstream, naked hemoglobin carries oxygen just as it does when in red cells. But while hemoglobin in red cells may last for six months, naked hemoglobin lasts only hours or days.

Still, such a short period is all the time needed in most uses. Transfusions are intended as only a temporary blood supply until the body makes more.

Rabbi Ben-yamin Walfish, director of the Rabbinical Council of America, said that blood substitutes from pigs would probably raise no religious objections. In Judaism, pigs may be used for purposes other than eating, he said, and in any case, kosher rules are set aside in matters of life and death.